Exchange of P/V genes between two non-cytopathic simian virus 5 variants results in a recombinant virus that kills cells through death pathways that are sensitive to caspase inhibitors

J Gen Virol. 2006 Dec;87(Pt 12):3643-8. doi: 10.1099/vir.0.82242-0.

Abstract

The paramyxovirus Simian virus 5 (SV5) is largely non-cytopathic in human epithelial and fibroblast cells. WF-PIV has been described previously as a naturally occurring SV5 variant that encodes P and V proteins differing from the wild-type (WT) SV5 proteins in eight and five amino acid positions, respectively. In this study, it is shown that WF-PIV is like WT SV5 by being largely non-cytopathic in A549 lung epithelial cells. However, substitution of the WF-PIV P/V gene into the background of WT SV5 resulted in a hybrid virus (P/V-WF) that induced apoptotic cell death not seen with either of the parental viruses. The kinetics of HeLa cell killing and induction of apoptosis by the P/V-WF chimera differed from those of the previously described P/V-CPI- chimera by being slower and less extensive. HeLa cell killing by the P/V-WF chimera was effectively reduced by inhibitors of caspase-9, but not of caspase-8. These results demonstrate that an exchange of P/V genes from two non-cytopathic SV5 variants can produce apoptosis-inducing chimeras, and that the role of the SV5 P/V gene products in limiting apoptosis can be dependent on expression in the context of a native viral genome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Caspase Inhibitors*
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival*
  • Cytopathogenic Effect, Viral / genetics
  • Enzyme Inhibitors / pharmacology
  • Epithelial Cells / virology*
  • HeLa Cells
  • Humans
  • Parainfluenza Virus 5 / genetics
  • Parainfluenza Virus 5 / pathogenicity*
  • Phosphoproteins / genetics*
  • RNA-Binding Proteins
  • Recombination, Genetic*
  • Viral Proteins / genetics*
  • Viral Structural Proteins / genetics*

Substances

  • Caspase Inhibitors
  • Enzyme Inhibitors
  • P protein, Simian parainfluenza virus 5
  • Phosphoproteins
  • RNA-Binding Proteins
  • V protein, Simian parainfluenza virus 5
  • Viral Proteins
  • Viral Structural Proteins